Diabetes Metab J.  2015 Apr;39(2):95-113. 10.4093/dmj.2015.39.2.95.

Current Antiplatelet Treatment Strategy in Patients with Diabetes Mellitus

• Jung JH
• Tantry US
• Gurbel PA
• Jeong YH

• KMID: 1805892
• DOI: http://doi.org/10.4093/dmj.2015.39.2.95

Abstract

Patients with diabetes mellitus (DM) have accelerated atherosclerosis with an increased risk for atherothrombotic cardiovascular complications. A state of high platelet reactivity and activation, hypercoagulability (prothrombotic state) and a subdued response to standard antiplatelet agents may explain high rate of adverse cardiovascular events in patients with DM. Several antithrombotic treatment strategies have been developed to control the prothrombotic state in patients with DM: dose modification of commonly used agents; use of potent agents; and addition of a third antithrombotic drug (triple therapy) to commonly prescribed dual antiplatelet therapy of aspirin and a P2Y12 inhibitor. The present review aims to provide an overview of the current knowledge on platelet abnormalities in patients with DM, focusing on the challenges and perspectives of antiplatelet treatment strategies in this population.

Keyword

Aspirin; Atherothrombosis; Diabetes; Platelet; P2Y12 inhibitor

MeSH Terms

Aspirin
Atherosclerosis
Blood Platelets
Diabetes Mellitus*
Humans
Platelet Aggregation Inhibitors
Thrombophilia
Aspirin
Platelet Aggregation Inhibitors

Figure

• 

  Fig. 1 Proposed mechanism of atherothrombosis in diabetes mellitus [4,5]. PKC, protein kinase C; RAGE, receptor for advanced glycation endproducts; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PAI-1, plasminogen activator inhibitor-1; VSMC, vascular smooth muscle cell.

• 

  Fig. 2 Antiplatelet agents currently available or under development [9,10]. PAR, protease-activated receptor; TXA, thromboxane; COX-1, cyclooxygenase-1; PDE, phosphodiesterase; AC, adenylyl cyclase; ADP, adenosine diphosphate; cAMP, cyclic adenosine monophosphate; 5-HT2A, 5-hydroxytryptamine (serotonin) receptor 2A; VASP-P, vasodilator-stimulated phosphoprotein-phosphorylation; PKA, protein kinase A; GP, glycoprotein; TNF, tumor necrosis factor.

• 

  Fig. 3 Relationship between clinical benefit and bleeding risk according to absolute cardiovascular risk in primary prevention trials of aspirin. Adapted from Halvorsen et al. [13]. To examine the association between treatment effects of aspirin on cardiovascular events, major gastrointestinal bleeding, and total major bleeding according to the level of cardiovascular risk (per 100 person-years in the control arm), univariate inverse variance-weighted linear regressions of the risk difference was fitted for the outcome events per 100 person-years between the two experimental arms. The size of circles is proportional to the inverse of variance of the risk difference. Red arrow denotes the area where benefit likely equals risk, yellow area denotes area of prescription uncertainty, and green arrow denotes the area where benefit most likely exceeds risk. Continuous line=linear regression; dotted line=lower and higher 95% confidence interval. CV, cardiovascular; GI, gastrointestinal; SAPAT, Swedish Angina Pectoris Aspirin Trial; JPAD, Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes; PPP, Primary Prevention Project; HOT, Hypertension Optimal Treatment; WHS, Women's Health Study; BDT, British Doctors Trial; PHS, Physicians Health Study; AAA, Aspirin for Asymptomatic Atherosclerosis; TPT, Thrombosis Prevention Trial; POPAPDAD, prevention of progression of arterial disease and diabetes.

• 

  Fig. 4 Metabolic pathway of P2Y12 receptor inhibitors. Adapted from Levine et al., with permission from Nature Publishing Group [23]. MDR1, multidrug resistance protein 1; hCE, human carboxylesterase; CYP, cytochrome P450; ADP, adenosine diphosphate; GP, glycoprotein.

• 

  Fig. 5 Randomized clinical trials evaluating primary efficacy of intensified antiplatelet regimen versus clopidogrel in diabetic patients with acute coronary syndrome [22,37,39,56]. CI, confidence interval; CURRENT-OASIS 7, Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs-Optimal Antiplatelet Strategy for InterventionS; PCI, percutaneous coronary intervention; ACS, acute coronary syndrome; TRITON-TIMI 38, Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38; PLATO, platelet inhibition and patient outcomes.

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